LTβR controls thymic portal endothelial cells for haematopoietic progenitor cell homing and T-cell regeneration

• Published in: Nature communications Vol. 7; no. 1; p. 12369
• Main Authors: Shi, Yaoyao, Wu, Weiwei, Chai, Qian, Li, Qingqing, Hou, Yu, Xia, Huan, Ren, Boyang, Xu, Hairong, Guo, Xiaohuan, Jin, Caiwei, Lv, Mengjie, Wang, Zhongnan, Fu, Yang-Xin, Zhu, Mingzhao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.08.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 13/51; 631/250/1619/554; 631/250/232/2058; 631/250/98; Animals; Endothelial Cells - cytology; Endothelial Cells - metabolism; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Homeostasis; Humanities and Social Sciences; Lymphotoxin beta Receptor - metabolism; Mice, Inbred C57BL; multidisciplinary; Science; Science (multidisciplinary); Signal Transduction; T-Lymphocytes - cytology; T-Lymphocytes - metabolism; Thymus Gland - cytology; Tumor Necrosis Factor Ligand Superfamily Member 14 - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms12369

Continuous thymic homing of haematopoietic progenitor cells (HPCs) via the blood is critical for normal T-cell development. However, the nature and the differentiation programme of specialized thymic endothelial cells (ECs) controlling this process remain poorly understood. Here using conditional gene-deficient mice, we find that lymphotoxin beta receptor (LTβR) directly controls thymic ECs to guide HPC homing. Interestingly, T-cell deficiency or conditional ablation of T-cell-engaged LTβR signalling results in a defect in thymic HPC homing, suggesting the feedback regulation of thymic progenitor homing by thymic products. Furthermore, we identify and characterize a special thymic portal EC population with features that guide HPC homing. LTβR is essential for the differentiation and homeostasis of these thymic portal ECs. Finally, we show that LTβR is required for T-cell regeneration on irradiation-induced thymic injury. Together, these results uncover a cellular and molecular pathway that governs thymic EC differentiation for HPC homing. Lymphoid progenitors migrate from the bone marrow into the thymus to give rise to T and NK cell lineages. Here the authors characterize a lymphotoxin receptor beta-dependent population of thymic endothelial cells that guide lymphoid progenitor homing in the thymus.